Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models

Shin, Woo-Young; Shim, Do-Wan; Kim, Myong-Ki; Sun, Xiao; Koppula, Sushruta; Yu, Sang–Hyeun; Kim, Han-Bi; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

doi:10.1016/j.jep.2017.03.043

Cited by 32 publications

(17 citation statements)

References 18 publications

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“…Therefore, exploring novel agents that have regulatory activity on the NLRP3 inflammasome might be an ideal therapeutic strategy for the treatment of inflammasome-mediated inflammatory diseases. Enormous efforts have been made in drug discovery, and in particular, traditional medicines have been important resources for treating inflammatory disorders [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Kwak

Koppula

et al. 2018

Mediators of Inflammation

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Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1β levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.

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Section: Introductionmentioning

confidence: 99%

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Kwak

Koppula

et al. 2018

Mediators of Inflammation

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“…54 In terms of drug development, traditional Chinese medicine (TCM) is a major resource for the treatment of inflammatory diseases. 55 The development of anti-GA drugs with adequate tolerance and safety from TCM is gaining increasing attention. 56 Res exists abundantly in grapes, mulberries, peanuts, and Reynoutria japonica and is a drug with great potential against GA.…”

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confidence: 99%

Resveratrol Relieves Gouty Arthritis by Promoting Mitophagy to Inhibit Activation of NLRP3 Inflammasomes

Fan

Chen

Xiang-hui

et al. 2021

JIR

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Background: Gouty arthritis (GA) is a common inflammatory disease with pain caused by the deposition of monosodium urate (MSU) crystals into joints and surrounding tissues. Resveratrol (Res), derived from grapes and peanuts and the traditional Chinese medicine (TCM) Reynoutria japonica for GA, acts against oxidation and inflammation. The present study aimed to investigate the therapeutic effect and mechanism of Res on GA. Methods: Arthritis rat models, MSU-induced peritonitis mouse models, and inflammatory models of mouse bone marrow-derived macrophage (BMDM) were used in this study. Enzyme-linked immunosorbent assay (ELISA), JC-1, histopathological, immunofluorescence, flow cytometry, Western blot methods were applied to observe the effects of resveratrol on NLRP3 inflammasomes and mitophagy. Results: Res significantly improves the gait score and synovitis of rats with GA and inhibits the peritoneal inflammation induced by MSU. Res inhibits the MSU-induced activation of NLRP3 inflammasomes by reducing the levels of IL-1β, IL-18, and Caspase-1 and the pyroptosis of macrophages. In addition, Res raises the level of mitochondrial membrane potential, inhibits the expression of P62 and Pink1, enhances the expressions of LC3B-II, Parkin, and TOMM20, and promotes mitophagy, while mitophagy inhibitors reverse the inhibitory effect of Res on the activation of NLRP3 inflammasomes. Conclusion:Res significantly improves GA, and the underlying mechanism might be inhibiting the activation of NLRP3 inflammasomes by triggering the Pink1/Parkin pathway to promote mitophagy.

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“…The recovered fluid was pelleted by centrifugation, and the total cells were counted. Subsequently, the cells were stained for both APC-conjugated F4/80 (17-4801) and FITC-conjugated Ly-6G (11-5931) antibodies (eBioscience) 47 and analyzed using flow cytometry (BD San Diego, CA, USA). The number of neutrophils was calculated as total cells multiplied by the percentage of Ly-6G positive and F4/80 negative cells.…”

Section: Methodsmentioning

confidence: 99%

BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination

Shim

Shin

et al. 2017

Sci Rep

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The ATPase activity of NLRP3 has pivotal role in inflammasome activation and is recognized as a good target for the development of the NLRP3 inflammasome-specific inhibitor. However, signals in the vicinity of the ATPase activity of NLRP3 have not been fully elucidated. Here, we demonstrate NLRP3 inflammasome-specific action of a benzoxathiole derivative, BOT-4-one. BOT-4-one exhibited an inhibition of NLRP3 inflammasome activation, which was attributable to its alkylating capability to NLRP3. In particular, the NLRP3 alkylation by BOT-4-one led to an impaired ATPase activity of NLRP3, thereby obstructing the assembly of the NLRP3 inflammasome. Additionally, we found that NLRP3 alkylators, including BOT-4-one, enhance the ubiquitination level of NLRP3, which might also contribute to the inhibition of NLRP3 inflammasome activation. Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.

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Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models

Cited by 32 publications

References 18 publications

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Resveratrol Relieves Gouty Arthritis by Promoting Mitophagy to Inhibit Activation of NLRP3 Inflammasomes

BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination

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